Abstract
Previous studies have implicated protein kinase C (PKC) in colon carcinogenesis, but a clear understanding of the role of PKC in colon cancer is lacking. The purpose of this study was to investigate the effects of dexniguldipine hydrochloride (DNIG) on the in vitro growth of HT-29 human colon carcinoma cells and the expression of PKC isoforms. DNIG is a selective inhibitor of PKC that binds specifically to the regulatory region and is also a potent antineoplastic drug with an ability to reverse multidrug resistance. DNIG (1.6-25 mu M) decreased the number of HT-29 cells in culture in a time- and dose-dependent manner with an EC(50) of 1.4 mu M on day 3. Predominant PKC isoforms expressed in HT-29 cells were identified as Delta and zeta by immunoblotting. The expression of PKC Delta and zeta was inhibited significantly by DNIG (0.16-1.25 mu M). These results suggest that the suppression of the growth of HT-29 colon carcinoma cells by DNIG involves the inhibition of the expression of PKC Delta and zeta.
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